1.3.2 Antigen Recognition in the Adaptive Immune System Flashcards
What are some basic characteristics of BCRs and TCRs?
Each BCR/TCR recognizes one antigen with high affinity and ALL BCRs/TCRs on a given cell are identical
What is an antigen?
Any substance that can bind specifically to an antibody or TCR
Immunogen?
An antigen capable of eliciting an immune response
What is an epitope/antigenic determinant?
Portion of the antigen that binds to the Ab or TCR
What does the term monoclonal mean?
A lymphocyte mediated immune response in which all involved lymphocytes are derived from a single clone
What does the term polyclonal mean?
a lymphocyte mediated immune response in which all involved are derived from multiple clones
What is cross-reactivity?
The binding of an antigen by an antibody or TCR specific for another antigen
What is an example of cross-reactivity?
Ex. Antibodies against Streptococcal M protein can cross react with myocardial antigens
Dimer – alpha/beta – mostly in lymphoid tissue, Transmembrane proteins, One ligand-binding region are characteristics of a TCR or BCR?
TCR
Presented on MHC and is primarily peptides and can be anywhere within the protein and must be sequential amino acids are characteristics of the antigens presented to TCRs or BCRs?
TCRs
Dimer of dimers – two heavy and two light chains, transmembrane or soluble, two ligand binding regions are characteristic of a TCR or BCR?
BCR
Native antigen which can be proteins, lipids, polysaccharides, or DNA and must be on the surface of Ag and can be sequential residues or residue brought together by conformation are characteristics of the antigens presented to TCRs or BCRs?
BCR
What is a super-antigen?
Microbial antigen that cross-link TCR and MHC independently of antigen specificity, outside of the peptide binding groove
What can a super antigen result in?
This leads to poly-clonal T cell responses which can lead to a cytokine storm
What are some possible sources of super antigens?
Staphylococcus, streptococcus, mycoplasma, Epstein Barr virus, and Rabies
Determination of whether a BCR is soluble or membrane bound is determined by what?
splicing of the mRNA
What are the two chains of the BCR?
Heavy and light chain
What are the two regions of the heavy and light chain?
Variable and constant regions
The complementary determining region is also known as what?
The hypervariability region
The Fab region is?
The Ag-binding fragment
The FC region is?
Crystallizable
What provides the structure and flexibility of the hinge region?
Proline-rich regions provide the structure while the flexibility is provided by high levels of glycine
What is the importance of the flexibility of BCRs?
The hinge region can flex to allow binding Ag in different conformations. Binding Ag also induces conformation changes in the constant region enabling binding to complement or Fc receptors
What is the biggest antibody isotype?
IgM - Pentamer
What antibodies are rare in sera?
IgD and IgE
What antibody is most abundant in sera?
IgG
Antibody multimers are connected together by?
J-chains
What is affinity?
The strength with which a ligand interacts with a binding site
What is avidity?
The strength of a protein-protein interaction when multiple binding sites are possible
The heavy chain of a BCR genome contains what regions?
Variable (V), Diversity (D), and Joining (J)
What is the process of generating B cell diversity in the DNA?
Genomic DNA is re-arranged yielding different V(D)J conformations. D to J recombination occurs first which is followed by V to DJ. This process is mediated by V(D)J recombinase
RAG-1 and RAG-2 have what role?
These mediate combinatorial diversity
What is the role of TdT?
mediates junctional diversity by addition and subtraction of nucleotides at the coding joint
What are the components of the pro-B cell?
This cell expresses transmembrane Ig-alpha/beta
What are the components of the Pre-B cell?
This cell expresses heavy chain and surrogate light chain on the surface
What are the components of the Immature B cell?
have a heavy and light chain are ready for cross-linking for activation or death
What is allelic exclusion?
Recombination continues on both alleles until successful recombination or cell runs out of coding sequence. Successful recombination of one allele inhibits rearrangement of opposite allele
What is re-activated with progression from the Pre-BCR to the BCR?
Re-expression of RAG-1/2 but not TdT
What is positive selection of the BCR?
Can the newly formed BCR be expressed?
What is the process of negative selection of the BCR?
does the new BCR bind self-antigen with high affinity
What is BCR editing?
If the BCR binds self-antigen then the auto specific B cell undergoes a second light chain rearrangement, after second light chain is added it will undergo another round of selection
What is clonal deletion?
if BCR editing does not succeed, cells will undergo apoptosis; cells that undergo positive selection become mature naïve B cells
What is the process of generating the pre-TCR?
Genomic DNA is re-arranged yielding different V(D)J conformations. D to J recombination occurs first which is followed by V to DJ. This process is mediated by V(D)J recombinase
Are RAG-1/2 and TdT used in TCR maturation?
Yes
What are T cell receptor excision circles (TRECs) and what are they used for?
circular DNA formed by the genomic rearrangement that occurs during V(D)J recombination. They are measured by qPCR and can be used in a diagnostic setting to determine thymic output after HSCT.
What is a double negative T cell?
this is where the alpha/beta or gamma/delta lineage is decided; and CD3 Pre-TCR is expressed. There is no CD4 or CD8 expressed
What is a double positive T cell?
TCR, CD4 and CD8 is expressed; T cell will then go through positive and negative selection to determine lineage
What is a single positive T cell?
The cell expresses TCR and either CD4 or CD8
What is positive selection in regards to T cells?
TCR binds MHC – peptide complexes in the thymus and only cells that express a TCR that can bind MHC-peptide complexes will be positively selected for
What is negative selection in regards to T cells?
TCR binds MHC-peptide complexes in the thymus resulting in the elimination of autoreactive T cells; preventing production of disease causing T cells. This is determined by the strength of binding. Weak MHC binding will be selected for. Strong binding of MHC will result in T cell death
What do NKT cells recognize?
These recognize glycolipids presented by CD1
What do gamma/delta T cells recognize?
These recognize small molecules without MHC
What is the first step in T cell maturation?
Early thymic progenitors migrate to the thymus
After migrating to the thymus what is the next step in the maturation process?
Cells enter the thymus at the cortico-medullary junction and migrate through the cortex before moving to the medulla
What happens to T cells in the cortex?
These mature from double negative to double positive T cells
What occurs to T cells in the medulla?
These are selected to be CD4 or CD8 cells
What is this an image of and what is each arrow pointing at?
This is an infants thymus. The top arrow is pointing at the lighter staining medulla, the middle arrow is pointing at the darker staining dense cortex, and the bottom arrow is the dense connective tissue capsule that surrounds the thymus.
What is this an image of and what are the arrows pointing at?
This is an infant thymus, and the arrows are pointing at Hassall corpuscles.
What is this an image of and what does each letter label?
This is an adult thymus. There is fewer lymphocytes present. CT = connective tissue; A = adipose tissue; and L = Lymphoid tissue.
How would you describe this image of flow cytometry in T cell development?
This image displays a normal development of T cells
This image shows what type of T cell development?
This is normal
How would you describe this image in regards to T cell development?
Pt 1 - Pediatric T-cell acute lymphoblastic leukemia
Most T-cells are double negative and have almost no CD3
How would you describe this image in regards to T cell development?
Pediatric T-cell acute lymphoblastic leukemia have almost all double positive Lacks CD3 as well. Later even in T cell development may have gone awry.
Lambda and kappa are two regions of what?
Light chains of BCRs
